Progression of Alzheimer's disease, tau propagation, and its modifiable risk factors

The number of patients with Alzheimer's disease (AD) has been increasing exponentially side by side with aging societies worldwide. Symptoms of AD worsen over time due to progressive neurodegeneration, requiring institutional care at the later stage and resulting in a heavy burden on patients, caregivers, and the public-health system. AD neuropathology is characterized by cerebral accumulation and aggregation of amyloid-β (Aβ) and tau proteins. For decades, Aβ has been a leading target in the therapeutic development for AD, and many drug candidates have been tested in clinical trials; however, most medications have failed to slow the progression of the disease. Tau pathology currently is attracting more attention as an alternate target for developing disease-modifying therapy. Tau is known to spread in a hierarchical pattern in AD brain, likely by trans-synaptic tau transfer between neurons. Extracellular tau may mediate tau spreading and serve as biomarker for AD. AD pathogenesis is multifactorial, and many genetic- and non-genetic factors are known to contribute to Aβ- and tau-related pathology. Recent studies indicate an association between vascular risk factors and AD. Identifying modifiable risk factors for AD and understanding their contributory mechanisms could be key in tackling this devastating disease.